Résumé : BACKGROUND: Serotonin receptors may play an important role in the pathophysiology of affective disorders. We studied type-2 serotonin (5-HT2) receptors in the brain of patients with major depression. METHOD: Using positron emission tomography (PET) and the selective radioligand [18F]altanserin, we investigated 5-HT2 receptor distribution in eight drug-free unipolar depressed patients and 22 healthy subjects. Data were analysed using Statistical Parametric Mapping 95. RESULTS: In depressed patients, [18F]altanserin uptake was significantly reduced in a region of the right hemisphere including the posterolateral orbitofrontal cortex and the anterior insular cortex. A trend to similar changes was found in the left hemisphere. No correlation was found between the uptake and the Hamilton rating scale score. CONCLUSIONS: Pathophysiology of depression may involve changes in 5-HT2 receptor in brain regions selectively implicated in mood regulation.